Improving hepatitis B screening and vaccination rates in a veterans affairs resident-based primary care clinic.

INTRODUCTION: In 2022, the Advisory Committee on Immunization Practices (ACIP) updated its recommendation regarding hepatitis B vaccination and advised vaccination for all adults aged 19-59 regardless of risk factors and those 60 years and older with risk factors. Adults 60 years and older without known risk factors may also be vaccinated. Our project aimed to spread awareness of the updated hepatitis B virus (HBV) vaccination guideline and improve HBV vaccination rates among veterans in a resident-based primary care clinic. METHODS: Preintervention data were collected from October to December 2021 and post intervention data were collected from March to May 2022; patients seen in the clinic during these months were included. Patients were considered immune against HBV if they had positive anti-hepatitis B surface antigen and susceptible to infection if the hepatitis B panel was negative. Interventions included educating each resident group regarding current guidelines via multifaceted modalities. In addition, a reminder for checking hepatitis B status was embedded in the veterans affairs (VA) electronic medical record. RESULTS: In the preintervention period from October to December 2021, a total of 1242 veterans were seen. 532 veterans had previous screening for hepatitis B immunity in the chart with 378 veterans negative for hepatitis B surface antibody. Of those 378 veterans, only 35 were vaccinated against hepatitis B during the time period studied. In the postintervention period, 1174 veterans were seen and 559 had prior hepatitis B immunity screening with 430 veterans negative for hepatitis B surface antibody. Of the 430 veterans with no immunity against HBV, 123 received hepatitis B vaccination during the time period studied, which is an increase of greater than 20% in the number of veterans vaccinated. DISCUSSION: Our data suggest that HBV vaccination rate was suboptimal among the veteran population. A low-cost intervention could be beneficial in integrating new vaccination guidelines in the VA standard of care. Increased awareness of the updated HBV vaccination guideline would likely help to achieve the goal of full vaccination among the veteran population.

Implementing a Financial Decision-Making Scale in APS Financial Exploitation Investigations: Use of the PARIHS Conceptual Framework.

BACKGROUND AND OBJECTIVES: Adult protective services (APS) agencies investigate cases of financial exploitation, and a critical aspect of such investigations is often the assessment of decision-making abilities. This study examined APS workers' implementation of a 10-item financial decision-making screening tool, the Financial Decision Tracker (FDT), across a 34-month period: pre-COVID-19, throughout COVID-19 restrictions, and for 1 year following the restrictions. RESEARCH DESIGN AND METHODS: Using the Promoting Action in Research Implementation in the Health Services implementation science conceptual framework, we examined aspects of context, facilitation, and evidence to determine how well APS workers were trained, certified, and skilled in using the FDT. Using individual and group interviews, we assessed factors often related to successful implementation (context and facilitation) and measured the number of scales used, the types of decisions under investigation, and how the tool's scoring system aligned with the APS workers' final ratings (evidence). RESULTS: Overall, implementation was sustained throughout the 34-month period. However, during COVID-19 restrictions, usage dropped to a rate 58% below that prior to and following the restrictions. A total of 839 scales were administered. Individuals with no decision-making deficits were slightly older (78.7 vs 77.1 years; t(837) = 2.54, p = .01) and had completed high school at a significantly higher rate (69% vs 59%, χ 2(1) = 5.20, p = .023) than those who had decision-making deficits. DISCUSSION AND IMPLICATIONS: Overall, the implementation trial can be considered a success. The FDT was used so often and effectively that it is now an APS best practices tool, meaning that in audits, the correct use of the FDT will be assessed.

Beer Potomania: Why Initial Fluid Resuscitation May Be Harmful.

Beer potomania is one of the less common causes of hyponatremia that we encounter. Patients usually have a recent history of binge drinking along with poor diet. The low solute content in alcoholic beverages limits daily urine output, and ingestion of extra fluid will cause dilutional hyponatremia as a result. Blindly providing intravenous fluid without an underlying cause of the hyponatremia can be detrimental, such as in patients with beer potomania. In our case, a patient presented to the emergency department due to poor oral intake from jaw pain and was found to be hyponatremic from alcohol intake. He initially received 2 liters of fluid, which caused overcorrection of his sodium, requiring more free water to lower his sodium as a result.

The Coronavirus Disease 2019 Pandemic Impacts Burnout Syndrome Differently Among Multiprofessional Critical Care Clinicians-A Longitudinal Survey Study.

OBJECTIVES: To determine the impact of coronavirus disease 2019 on burnout syndrome in the multiprofessional ICU team and to identify factors associated with burnout syndrome. DESIGN: Longitudinal, cross-sectional survey. SETTING: All adult ICUs within an academic health system. SUBJECTS: Critical care nurses, advanced practice providers, physicians, respiratory therapists, pharmacists, social workers, and spiritual health workers were surveyed on burnout in 2017 and during the coronavirus disease 2019 pandemic in 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Burnout syndrome and contributing factors were measured using the Maslach Burnout Inventory of Health and Human Service and Areas of Worklife Survey. Response rates were 46.5% (572 respondents) in 2017 and 49.9% (710 respondents) in 2020. The prevalence of burnout increased from 59% to 69% (p < 0.001). Nurses were disproportionately impacted, with the highest increase during the pandemic (58-72%; p < 0.0001) with increases in emotional exhaustion and depersonalization, and personal achievement decreases. In contrast, although burnout was high before and during coronavirus disease 2019 in all specialties, most professions had similar or lower burnout in 2020 as they had in 2017. Physicians had the lowest rates of burnout, measured at 51% and 58%, respectively. There was no difference in burnout between clinicians working in ICUs who treated coronavirus disease 2019 than those who did not (71% vs 67%; p = 0.26). Burnout significantly increased in females (71% vs 60%; p = 0.001) and was higher than in males during the pandemic (71% vs 60%; p = 0.01). CONCLUSIONS: Burnout syndrome was common in all multiprofessional ICU team members prior to and increased substantially during the pandemic, independent of whether one treated coronavirus disease 2019 patients. Nurses had the highest prevalence of burnout during coronavirus disease 2019 and had the highest increase in burnout from the prepandemic baseline. Female clinicians were significantly more impacted by burnout than males. Different susceptibility to burnout syndrome may require profession-specific interventions as well as work system improvements.

Initiation, dropout, and outcome from evidence-based psychotherapies in a VA PTSD outpatient clinic.

Trauma-focused, evidence-based psychotherapies (TF-EBPs) for posttraumatic stress disorder (PTSD) have been widely promoted in the Veterans Health Administration to provide access to state-of-the-art treatments, but dropout rates may affect the impact of TF-EBPs. The current study summarizes findings from a program evaluation of 67 veterans assigned to trauma-focused treatment in a Veterans Affairs outpatient PTSD clinic. Outcomes of interest include attendance rates, dropout rates and patterns, treatment paths, changes in self-reported symptoms, and clinician ratings. Nine veterans (13.4%) did not attend a first session and 15 (22.4%) dropped out before session 4. Twenty-three (33.8%) received either a modified version of the TF-EBP or switched to a different treatment. Only 11 (16.4%) completed the assigned TF-EBP, but 10 of those 11 (90.9%) were rated by their therapist as improved. These results align with previous research documenting high dropout rates from PTSD treatment in veterans and substantial improvements for those who complete TF-EBPs. Future study of methods to enhance retention in TF-EBP treatments is needed. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

ENU mutagenesis in mice identifies candidate genes for hypogonadism.

Genome-wide mutagenesis was performed in mice to identify candidate genes for male infertility, for which the predominant causes remain idiopathic. Mice were mutagenized using N-ethyl-N-nitrosourea (ENU), bred, and screened for phenotypes associated with the male urogenital system. Fifteen heritable lines were isolated and chromosomal loci were assigned using low-density genome-wide SNP arrays. Ten of the 15 lines were pursued further using higher-resolution SNP analysis to narrow the candidate gene regions. Exon sequencing of candidate genes identified mutations in mice with cystic kidneys (Bicc1), cryptorchidism (Rxfp2), restricted germ cell deficiency (Plk4), and severe germ cell deficiency (Prdm9). In two other lines with severe hypogonadism, candidate sequencing failed to identify mutations, suggesting defects in genes with previously undocumented roles in gonadal function. These genomic intervals were sequenced in their entirety and a candidate mutation was identified in SnrpE in one of the two lines. The line harboring the SnrpE variant retains substantial spermatogenesis despite small testis size, an unusual phenotype. In addition to the reproductive defects, heritable phenotypes were observed in mice with ataxia (Myo5a), tremors (Pmp22), growth retardation (unknown gene), and hydrocephalus (unknown gene). These results demonstrate that the ENU screen is an effective tool for identifying potential causes of male infertility.

Evaluating the clinical efficacy of a primary care-focused, nurse-led, consultation liaison model for perinatal mental health.

In Australia, perinatal mental illness is common, although poorly identified and treated. Improved perinatal mental health depends on service provision models that reflect a focus on promotion, prevention, and early intervention, while facilitating improved referral pathways between primary health and specialist mental health services. In 2008, a contemporary community-based model of mental health service provision was developed as an alternative to the pre-existing hospital-based service model. The model is delivered primarily by mental health nurses using a consultation liaison framework. It provides for specialist mental health assessment and brief intervention in collaboration with the general practitioner, who remains the primary health provider. It also aims to raise community awareness and build capacity for the management of perinatal disorders in the primary care sector. Evaluation of the clinical effectiveness of the model, and the improvement in access for primary health providers and women, was conducted at 2 years from its implementation. Clinical effectiveness was evaluated by using comparative data from the Edinburgh Depression Scale and Depression Anxiety and Stress Scale, and the results demonstrated clinical efficacy. Improved attendance rates indicated that women preferred this community-based service model as an alternative to the pre-existing service model.

A missense mutation in LRR8 of RXFP2 is associated with cryptorchidism.

Using genome-wide mutagenesis with N-ethyl-N-nitrosourea (ENU), a mouse mutant with cryptorchidism was identified. Genome mapping and exon sequencing identified a novel missense mutation (D294G) in Relaxin/insulin-like family peptide receptor 2 (Rxfp2). The mutation impaired testicular descent and resulted in decreased testis weight in Rxfp2 ( DG/DG ) mice compared to Rxfp2 (+/DG ) and Rxfp2 (+/+) mice. Testicular histology of the Rxfp2 ( DG/DG ) mice revealed spermatogenic defects ranging from germ cell loss to tubules with Sertoli-cell-only features. Genetic complementation analysis using a loss-of-function allele (Rxfp2 (-)) confirmed causality of the D294G mutation. Specifically, mice with one of each mutant allele (Rxfp2 ( DG/-)) exhibited decreased testis weight and failure of the testes to descend compared to their Rxfp2 (+/-) littermates. Total and cell-surface expression of mouse RXFP2 protein and intracellular cAMP accumulation were measured. Total expression of the D294G protein was minimally reduced compared to wild-type, but cell-surface expression was markedly decreased. When analyzed for cAMP accumulation, the EC50 was similar for cells transfected with wild-type and mutant RXFP2 receptor. However, the maximum cAMP response that the mutant receptor reached was greatly reduced compared to the wild-type receptor. In silico modeling of leucine rich repeats (LRRs) 7-9 indicated that aspartic acid 294 is located within the ß-pleated sheet of LRR8. We thus postulate that mutation of D294 results in protein misfolding and aberrant trafficking. The ENU-induced D294G mutation underscores the role of the INSL3/RXFP2-mediated pathway in testicular descent and expands the repertoire of mutations known to affect receptor trafficking and function.

Identification of chemically diverse Chk1 inhibitors by receptor-based virtual screening.

Inhibition of the Chk1 kinase by small molecules is of great therapeutic interest for oncology and in understanding the cellular regulation of the G2/M checkpoint. We report how computational docking of a large electronic catalogue of compounds to an X-ray structure of the Chk1 ATP-binding site allowed prioritisation of a small subset of these compounds for assay. This led to the discovery of 10 novel Chk1 inhibitors, distributed among nine new and clearly different chemical scaffolds. Several of these scaffolds have promising lead-like properties. All these ligands act by competitive binding to the targeted ATP site. The crystal structures of four of these compounds bound to this site are presented, and reasonable modelled docking modes are suggested for the 5 other scaffolds. This structural context is used to assess the potential of these scaffolds for further medicinal chemistry efforts, suggesting that several of them could be elaborated to make additional interactions with the buried part of the ATP site. Some unusual interactions with the conserved kinase backbone motif are pointed out. The ligand-binding modes are also used to discuss their medicinal chemistry potential with respect to undesirable chemical functionalities, whether these functionalities bind directly to the protein or not. Overall, this work illustrates how virtual screening can identify a diverse set of ligands which bind to the targeted site. The structural models for these ligands in the Chk1 ATP-binding site will facilitate further medicinal chemistry efforts targeting this kinase.

The whole truth: comparative analysis of diaphragmatic hernia repair using 4-ply vs 8-ply small intestinal submucosa in a growing animal model.

BACKGROUND: Diaphragmatic reconstruction remains a challenging problem. There is limited information concerning the use of small intestinal submucosa (SIS) in congenital diaphragmatic hernia repair. A canine model was used to evaluate the use of a SIS patch in diaphragmatic reconstruction. METHODS: Eleven beagle puppies (1.6-4.2 kg, 8 weeks old) underwent left subcostal laparotomy, central left hemidiaphragm excision (2 x 7 cm, 50% loss), and reconstruction with a 4-ply group I (n = 5) or 8-ply group II (n = 6) SIS patch. Chest radiographs were taken at time of operation and 3 and 6 months postoperatively. Animals were killed at 6 months. Adhesion formation (both pleural and abdominal), gross visual evaluation of the patch, and histology were compared. RESULTS: In group I (4-ply), 1 animal died at 3 months from patch deterioration accompanied by stomach herniation that resulted in respiratory failure. In the 4 remaining animals, chest radiographs showed no evidence of herniation or eventration. On physical examination, there was no evidence of chest wall deformity. During gross surgical examination, the 4-ply patches showed thinning, multiple defects, and liver herniation in 3 animals. In 1 pup, the patch was thickened, intact, well incorporated at the repair site, and adherent to the liver and spleen. In group II (8-ply), 1 animal died of cardiopulmonary failure in the early postoperative period. In the other 5 animals, chest radiographs showed evidence of eventration in 1. On gross examination the patch adhered to the liver in all 5 surviving animals. In 4, the patches were thickened, viable, but had some shrinkage. One patch pulled away from the native diaphragm laterally; however, no visceral herniation was present. In the 1 animal with eventration, there was no evidence of a patch. Adhesion scores (AS) were graded and determined by the sum of extent (0-4), type (0-4), and tenacity (0-3). Average abdominal AS in group I was 5.6 +/- 0.8 vs 10.2 +/- 0.2 (P = .079) for group II. Average lung AS was 0.6 +/- 0.6 in group I vs 3.8 +/- 1.1 (P = .0476) for group II. Histological examination showed group II patches had greater collagen deposition with central calcification and mild inflammation within the residual graft, whereas group I patches were much thinner and were composed of granulation tissue without evidence of residual graft. CONCLUSIONS: These data indicate that 8-ply SIS repair of diaphragmatic defects was superior (80%; 4/5 to 4-ply, 20%; 1/5, success). Organ adherence appears to be necessary for neovascularization of the SIS composite. Eight-ply grafts appear to be more durable and persist for a longer period, which may improve neovascularization. Long-term follow-up to evaluate remodeling characteristics of the patch material is required.

Identification of a buried pocket for potent and selective inhibition of Chk1: prediction and verification.

Inhibition of the Chk1 kinase by small molecules binding to its active site is a strategy of great therapeutic interest for oncology. We report how computational modelling predicted the binding mode of ligands of special interest to the Chk1 ATP site, for representatives of an indazole series and debromohymenialdisine. These binding modes were subsequently confirmed by X-ray crystallography. The binding mode of a potent indazole derivative involves non-conventional C-H...O and N-H...pi-aromatic interactions with the protein. These interactions are formed in a buried pocket at the periphery of the ATP-binding site, the importance of which has previously been overlooked for ligand design against Chk1. It is demonstrated that filling this pocket can confer ligands with dramatically enhanced affinity for Chk1. Structural arguments in conjunction with assay data explain why targeting this pocket is also advantageous for selective binding to Chk1. Structural overlays of known inhibitors complexed with Chk1 show that only the indazole series utilizes the pocket of interest. Therefore, the analysis presented here should prove helpful in guiding future structure-based ligand design efforts against Chk1.

Structure-based design of novel Chk1 inhibitors: insights into hydrogen bonding and protein-ligand affinity.

We report the discovery, synthesis, and crystallographic binding mode of novel furanopyrimidine and pyrrolopyrimidine inhibitors of the Chk1 kinase, an oncology target. These inhibitors are synthetically tractable and inhibit Chk1 by competing for its ATP site. A chronological account allows an objective comparison of modeled compound docking modes to the subsequently obtained crystal structures. The comparison provides insights regarding the interpretation of modeling results, in relationship to the multiple reasonable docking modes which may be obtained in a kinase-ATP site. The crystal structures were used to guide medicinal chemistry efforts. This led to a thorough characterization of a pair of ligand-protein complexes which differ by a single hydrogen bond. An analysis indicates that this hydrogen bond is expected to contribute a fraction of the 10-fold change in binding affinity, adding a valuable observation to the debate about the energetic role of hydrogen bonding in molecular recognition.

Comparison of treatment for post-traumatic stress disorder among three Department of Veterans Affairs medical centers.

The objective of the present study was to compare three specialized treatment programs for post-traumatic stress disorder (PTSD) in different Veterans Affairs medical centers, in terms of the format of therapeutic services and the medications prescribed for PTSD. Chart review methods were used to examine medical records for 50 patients from each facility over a 6-month period. Results indicated that the medications prescribed were fairly consistent across sites, although they were not always consistent with treatment recommendations. Therapy formats for two of the facilities were quite different, with one offering more case management services and the other offering more intensive individual and group therapy services. Additional research is needed to broaden our knowledge of how PTSD is being treated currently and to study the effectiveness of the treatment strategies being used.

Acetylcholine-secreting cells improve age-induced memory deficits.

The present study examined whether aged rats with naturally occurring cognitive deficits in spatial learning and memory would benefit from local chronic supplementation of acetylcholine. Aged impaired and aged unimpaired rats were pretested in the water maze to characterize the extent of age-induced cognitive impairment. Groups were matched for extent of deficits. The animals subsequently received implants of either acetylcholine-releasing cells or control cells into the cortical and hippocampal target regions of the basal forebrain. One week postgrafting, spatial learning and memory were retested using the same behavioral procedure. All aged groups acquired the platform position more slowly than young controls. However, aged impaired rats grafted with acetylcholine-releasing cells performed significantly better than aged impaired rats with control grafts, and they did not differ from aged unimpaired groups. A spatial memory probe test revealed that memory for the escape platform location of the acetylcholine-grafted rats was significantly better than that of rats with control grafts and matched the performance of young controls. In vitro, biochemical and electrophysiological analyses of the engineered cells confirmed choline acetyltransferase activity and showed quantal release of acetylcholine from the transduced cells. In vivo, RT-PCR of microdissected grafts indicated that the engineered cells expressed the choline acetyltransferase transgene for up to 40 days postgrafting. These results indicate that locally restricted supplementation of acetylcholine into the two major target regions of the cholinergic basal forebrain of aged impaired rats ameliorates some age-related cognitive deficits.

Intravenous catheter training system: computer-based education versus traditional learning methods.

BACKGROUND: Virtual reality simulators allow trainees to practice techniques without consequences, reduce potential risk associated with training, minimize animal use, and help to develop standards and optimize procedures. Current intravenous (IV) catheter placement training methods utilize plastic arms, however, the lack of variability can diminish the educational stimulus for the student. This study compares the effectiveness of an interactive, multimedia, virtual reality computer IV catheter simulator with a traditional laboratory experience of teaching IV venipuncture skills to both nursing and medical students. METHODS: A randomized, pretest-posttest experimental design was employed. A total of 163 participants, 70 baccalaureate nursing students and 93 third-year medical students beginning their fundamental skills training were recruited. The students ranged in age from 20 to 55 years (mean 25). Fifty-eight percent were female and 68% percent perceived themselves as having average computer skills (25% declaring excellence). The methods of IV catheter education compared included a traditional method of instruction involving a scripted self-study module which involved a 10-minute videotape, instructor demonstration, and hands-on-experience using plastic mannequin arms. The second method involved an interactive multimedia, commercially made computer catheter simulator program utilizing virtual reality (CathSim). RESULTS: The pretest scores were similar between the computer and the traditional laboratory group. There was a significant improvement in cognitive gains, student satisfaction, and documentation of the procedure with the traditional laboratory group compared with the computer catheter simulator group. Both groups were similar in their ability to demonstrate the skill correctly. CONCLUSIONS; This evaluation and assessment was an initial effort to assess new teaching methodologies related to intravenous catheter placement and their effects on student learning outcomes and behaviors. Technology alone is not a solution for stand alone IV catheter placement education. A traditional learning method was preferred by students. The combination of these two methods of education may further enhance the trainee's satisfaction and skill acquisition level.